Synthesis and Assessment of Peptide Gd-DOTA Conjugates Targeting Extradomain B Fibronectin for Magnetic Resonance Molecular Imaging of Prostate Cancer.
Synthesis and Assessment of Peptide Gd-DOTA Conjugates Targeting Extradomain B Fibronectin for Magnetic Resonance Molecular Imaging of Prostate Cancer.
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DOI：
10.1021/acs.molpharmaceut.7b00619
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发表时间：
2017-11-06
影响因子：
4.9
通讯作者：
Lu ZR
中科院分区：
文献类型：
--
作者：
Li Y;Han Z;Roelle S;DeSanto A;Sabatelle R;Schur R;Lu ZR
对比增强MRI通常用于前列腺癌的成像和治疗计划。然而，没有肿瘤靶向造影剂可用于MRI准确检测和表征前列腺癌。结构域外B纤连蛋白（EDB-FN）是一种存在于侵袭性肿瘤中的癌蛋白，是检测和分层高危前列腺癌的一个有前途的分子靶点。在这项工作中，我们已经确定了四个小肽（GVK，IGK，SGV和ZD 2）特异性EDB-FN的肿瘤靶向。肽与EDB蛋白片段的结合模式和亲和力的计算机模拟揭示了配体-受体相互作用中不同肽的不同结合位点。在携带PC-3人前列腺癌异种移植物的雄性小鼠中使用荧光成像评估肽的肿瘤特异性和器官分布。通过将四氮杂环十二烷-1，4，7，10-四乙酸（DOTA）与固相中的肽缀合，然后与GdCl 3络合来合成靶向造影剂。通过MALDI-TOF质谱和弛豫率测量对造影剂进行表征。所有四种肽Gd-DOTA缀合物在PC 3小鼠前列腺癌模型的MR成像中导致稳健的肿瘤对比度增强。对EDB-FN具有特异性的肽Gd-DOTA缀合物是用于前列腺癌MR分子成像的有希望的靶向小分子大环造影剂。
Contrast enhanced MRI is commonly used in imaging and treatment planning of prostate cancer. However, no tumor targeting contrast agent is commercially available for accurate detection and characterization prostate cancer with MRI. Extradomain B fibronectin (EDB-FN), an oncoprotein present in aggressive tumors, is a promising molecular target for detection and stratification of high-risk prostate cancer. In this work, we have identified four small peptides (GVK, IGK, SGV, and ZD2) specific to EDB-FN for tumor targeting. In-silico simulations of the binding patterns and affinities of peptides to the EDB protein fragment revealed different binding site to different peptide in the ligand-receptor interactions. Tumor specificity and organ distribution of the peptides were assessed using fluorescence imaging in male mice bearing PC-3 human prostate cancer xenografts. Targeted contrast agents were synthesized by conjugating tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to the peptides in the solid phase, followed by complexation with GdCl3. The contrast agents were characterized by MALDI-TOF mass spectrometry and relaxivity measurements. All four peptide Gd-DOTA conjugates resulted in robust tumor contrast enhancement in MR imaging of the PC3 mouse prostate cancer model. The peptide Gd-DOTA conjugates specific to EDB-FN are promising targeted small molecular macrocyclic contrast agents for MR molecular imaging of prostate cancer.
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DOI：
10.1007/s00259-016-3346-0
发表时间：
2016-07
影响因子：
9.1
作者：
Giesel FL;Sterzing F;Schlemmer HP;Holland-Letz T;Mier W;Rius M;Afshar-Oromieh A;Kopka K;Debus J;Haberkorn U;Kratochwil C
通讯作者：
Kratochwil C
影响因子：
7.3
作者：
Banerjee SR;Pullambhatla M;Byun Y;Nimmagadda S;Green G;Fox JJ;Horti A;Mease RC;Pomper MG
通讯作者：
Pomper MG
影响因子：
2.1
作者：
Durmus, Tahir;Reichelt, Uta;Franiel, Tobias
通讯作者：
Franiel, Tobias
DOI：
10.1056/nejmoa1311593
发表时间：
2014-03-06
期刊：
The New England journal of medicine
影响因子：
--
作者：
Bill-Axelson A;Holmberg L;Garmo H;Rider JR;Taari K;Busch C;Nordling S;Häggman M;Andersson SO;Spångberg A;Andrén O;Palmgren J;Steineck G;Adami HO;Johansson JE
通讯作者：
Johansson JE
影响因子：
--
作者：
Jankovic, Miroslava M.;Kosanovic, Maja M.
通讯作者：
Kosanovic, Maja M.